We're all familiar with what it is like to be sick. Symptoms of disease can be general, such as feeling tired, or chilled. Or localized, such as having a runny nose. Those symptoms can appear suddenly, or progress over a couple of days. And they can vary in how incapacitating they are from mild to severe. All of the features that you experience when you have a disease occur, because of structural or functional changes in molecules, in the cells, that make up your tissues. These changes result from physical or metabolic injury to the cell that prevents it from functioning correctly. Infection with a pathogenic microorganism can initiate these changes. Scientists working in infectious disease study the sequence of events and mechanisms that lead to the symptoms of a disease. The disease caused by different microorganisms progressed differently, but there are also some steps that are common. These general steps involve a localized vascular response, alteration and damage to cells in the tissue, and cleanup and repair of the damage to restore proper function. We'll briefly review these steps as they relate to the short list symptoms of the disease we usually experience. The vascular responses that occur with an infection are the early stages of the inflamatory process. Local tissue damage or a pathogen infecting a cell. Can elicit the signals that set off the inflammatory response. Think about how quickly the area around a splinter gets red and swollen, feels warm to the touch, and is painful. Cornelius Celsus in the first century A.D. described the inflammatory process. Giving the four features listed above their Latin names. Rubor (redness), tumor (swelling), calor (heat), and color (pain). These four signs are the results of changes in blood flow in local vessels. The redness in an inflamed tissue is just due to an increase in the amount of blood within vessels. And the area feels warmer, because the temperature of the blood is a little higher than the skin temperature. With the increased vascular pressure, some fluid can leak from the blood vessel into the tissue. This counts for the swelling and indirectly for the pain, because the swelling can put pressure on nerves. These early stages occur in minutes to hours of receiving the damaged signals. Increasing blood flow to an area allows cells that are circulating in the blood That will be responsible for stopping further injury and for fixing damage to get to the site. They exit the bloodstream at the location, sending the damage signals. The various cells that are recruited have different roles. The first that arrive can directly kill and remove a pathogen. Others kill infected cells to stop the infection from spreading. Later, other cells from the blood arrive that facilitate cleanup and repair of cells and the tissues directly damaged by the pathogen. The regulation of inflammation is critical. Because in the process of killing pathogens in infected cells There is inevitably some damage that occurs to surrounding uninfected cells. If inflammation is controlled and localized, which is the normal situation, the consequence of infection in most tissues are minor. Consider a virus infection in your nasal passages. The symptoms you experienced are from damage to the mucosal cells in the nose. And usually consist of sneezing, and a runny nose. After a few days, the virus is cleared, the fluid is absorbed. And the damaged cells are replaced, and your symptoms go away. There are many viruses that cause the upper respiratory tract infections we call a cold, and the symptoms you experience can vary in severity and duration. But the steps that lead to the disease all involve the vascular changes, movement of cells and fluid to the damaged site, and repair. Although the inflammatory process is absolutely required to stop an infection, it sometimes does so with excessive force. Cells are the functional units of our tissues, such as the lung. If many cells are damaged in a tissue, there can be serious consequences. For example, the effect of fluid leakage and loss of cells can be accommodated in a tissue like muscle or liver, but is problematic in lung and brain. Emerging virus infections, like the virus that causes SARS, have a clinical presentation of acute respiratory distress, because fluid accumulates in the lungs and impairs oxygen exchange. Fluid accumulation in the brain, or loss of nerve cells, can also lead to life threatening conditions. The cells that are recruited to the site of infection during the inflammation, might target normal uninfected cells for removal. Which can exasperate direct damage due to the pathogen. Thus the damage to tissues that leads to disease symptoms from some infections can also be due to our own defense strategies. To review, pathogens make us sick by direct damage to cells and the tissue. The damage sets off a series of events, the inflammatory process, to control the infection and repair damage. But if inflammation isn't properly regulated, there can be excessive damage to the tissue with serious loss of function that is from the inflammatory response itself.